According to the World Health Organization (WHO), 90% of the population suffers from dental caries and 80% prefers not to go to the dentist's office since they are afraid of local anesthesia and the sound produced by the turbine (drill), while describing the technique as negative and with a high degree of rejection, as they consider noise, vibration and pressure as obstacles to a comprehensive dental rehabilitation.
The technique of manual removal of the caries tissue appears as an alternative which offers greater comfort to patients of all ages. After carrying out some research on literature and clinical cases related to this issue, the action of a specific enzyme which synergistically works in the selective manual removal of the caries tissue is surprising, thus enhancing the technique and making it more amenable both for the patient and the dentist.
From the 70's on, several researchers have suggested different composition formulas for the removal of the dental caries, based on the principle of maximum preservation of the healthy dental structure.
In 1975, Habib et al. (Habib C. M., Kronman J., Goldman M., A chemical evaluation of collagen and hydroxyproline alter treatment with GK-101(N-chloroglycine). Pharmacol. Ther. Dent., v.2, 209-215, 1975) started this methodology by using 5% sodium hypochlorite having a non-specific proteolytic effect which removed the decayed dental tissue. However, it was a toxic, irritant agent for the mouth tissues and, for this reason, a solution was proposed which involved addition of glycine, sodium chloride and sodium hydroxide to the 5% sodium hypochlorite with the purpose of solving such inconvenience. The modified formula became known as GK-101 and consisted of N-monochloroglycine (Goldman M., Kronman J. H.; A preliminary report on a chemomechanical means of removing caries. J. Am. Dent. Assoc. 1976; 93(6):1149-53). Even though this made the process much more effective than hypochlorite alone, it was slower to remove the caries tissue. Furthermore, this process did not include adhesive dental materials to perform fillings, and therefore the use of turbines was still necessary to shape the cavities.
To the N-monochloroglycine comprising formula, aminobutyric acid was added, thus obtaining a composition marketed under the name Caridex (Schutzbank S. G., Galaini J., Kronman J. H., Goldman M., Clarke R. E. A. A Comparative in vitro study of the effect of GK-101 and GK 101E in caries removal. J. Dent. Res. 1978; 57:861-864). Even when it is more effective in disrupting the dentin collagen of the caries, Caridex had some clinical restrictions, among which we could mention: it had higher cost, it required a large vessel with a pump, it required large quantities of solution, it presented several problems during heating and it had a short shelf-life (Beeley J. A., Yip H. K., Stevenson A. G. Chemomechanical caries removal: a review of the techniques and latest developments. Br. Dent. J. 2000; 188:427-430).
In order to render it more effective and easier to handle, this Caridex gel evolved into the Carisolv system, which comprised two agents: a carboxymethylcellulose-based gel with a solution of three different amino acids: lysine, leucine and glutamic acid; the second component is a 0.5% sodium hypochlorite solution. Despite the advantages which were achieved, as are preservation of the healthy dental tissue and reduced use of rotating tools (Ericson D., Zimmerman M., Raber H., Gotrik B., Bornstein R., Thorell J.; Clinical evaluation of efficacy and safety of a new method for chemo-mechanical removal of caries. Caries Res. 1999; 33:171-177), the use of Carisolv could not be systematized, thus limiting its application to a small part of the population due to difficulties of usage such as the need for intensive training and professional records and the need for specific tools, which increased the cost of this solution.
With the aim to globalize the use of this chemical-mechanical system for removal of the dental caries, a gel-type product was launched to the market in 2003, which main component is papain, an enzyme obtained from the papaya, similar to human pepsin.
It was created in Brazil by two researchers, Dr. Sandra Kalil Bussadori, Pediatric Dentistry, Professor at Universities of Sao Paulo and Metropolitana de Santos and Dr. Márcia Bouças Miziara, from the pharmaceutical firm Fórmula & Ação Farmácia, and it was given the commercial name Papacarie.
Papacarie comprises papain as the active ingredient, chloramine T, carboxymethylcellulose, sodium chloride, methylparaben, sodium hydroxide, colorings and enough quantity of distilled water to complete the formulation (WO2005020946A1), which was improved later on with a gel composed by papain, chloramine T, pectin, polyethylene glycol, propylene glycol and coloring agents. (WO2014016644A1)
Papain is extracted from the latex of the leaves and fruits of the green adult papaya, Carica Papaya, which is grown in tropical countries such as Brazil, India, Ceylon, South Africa and Hawaii.
It is a proteolytic enzyme having bactericide, bacteriostatic and anti-inflammatory properties, working exclusively on the dental dead tissue since it does not contain plasmatic antiprotease α1-antitrypsin which inhibits the proteolytic action of the papain. Because of this, softening of the dead tissue occurs, thus debriding the collagen fibers which are partially degraded, while preserving the healthy tissue as it is not demineralized and it does not have any exposed collagen fibers.
Another component used in the Papacarie formulation is chloramine. It is composed by chlorine and ammonium which have bactericide and disinfectant properties used for the root canal irrigation. It is an additional chemical softener of the decayed dentin, so that the secondary and/or quaternary structure of the collagen is affected because hydrogen bonds are broken, which makes removal of the decayed tissue easier. When checking the effect of the chloramine by using scanning electron microscopy and Vickers microhardness, it was observed that the use of chloramine resulted in open dentinal tubules in the outer layer of the decayed dentin.
Chloramine is a component which is generally hazardous for human health. A few minutes after chloramine intake a person can suffer from sickness, cyanosis, circulatory collapse, foaming at the mouth and respiratory failure. Chloramine in water containers has caused methemoglobinemia and hemolysis in patients undergoing dialysis. It has also caused bronchospasm when inhaled.
Due to each of its components, Papacarie achieves a synergistic action which makes removal of the caries easier with highly antimicrobial properties and without using special dental tools.
Its major advantages are that it requires less manual pressure, causes less tiredness to the intervening professional and less sensitivity on the patient's behalf.
This gel is especially recommended for the following situations: asymptomatic deep carious lesions reducing the risk of pulp exposure in toddlers, children, adolescents and/or phobic adults or patients with special needs; removal of root caries; chemo-mechanical treatment of the root surface in periodontology, rendering removal of dental calculus or tartar and root isolation easier; and use in public health due to its affordable cost.
No contraindications are mentioned. Innumerable studies have shown that there is no irritation due to direct contact of the gel with the oral tissues. However, there are certain circumstances under which Papacarie should not be applied: when there are symptoms consistent with chronic infectious processes such as fistulas, spontaneous pain or pain on percussion, in patients with systemic diseases which may alter the host's immune response such as diabetes, blood dyscrasias, etc.
This product must be kept under proper cooling and must be removed from the refrigerator fifteen minutes before use in order to apply it at room temperature.
Another gel based on papain and pectin is described in Patent Application AR Number P20120101629, published as AR085779A1. Claim 1 of this document is directed to a chemical-dental formulation which removes the carious tissue, to a manufacturing process and mode of application of same for dental caries or carious tissue removal; characterized by comprising: between 2 and 6% of a proteolytic enzyme, preferably 30,000 U/mg papain; between 0.2 and 1% of an antifungal, preferably Chloramine T; between 0.1 and 0.3% of an antimicrobial coloring agent, preferably Toluidine blue; all the aforementioned components supported by a stabilizing agent, preferably citrus pectin, from 3 to 6% in deionized water, and adjustment to pH 5/7 with a dilute triethanolamine solution in deionized water.
Therefore, according to the current state of the art related to papain-pectin systems, the maximum obtained values for papain gels range from 600 to 1,800 U/mg (see Patent Application AR085779A1) and in the papain-propyleneglycol-polyethyleneglycol systems the maximum obtained values are approximately 600 U/mg (see WO2014016644A1).
Consequently, when evaluating the advantages and disadvantages of all the above mentioned systems, the conclusion is that it is advisable to have a papain-based enzymatic gel reformulated by improving the carrier means for this enzyme, one which is much more stable and has a greater power of action both on acute and chronic caries, one which also has a chronologically enhanced action, without the need for specific tools and avoiding use of potentially toxic products.